Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001133426p
Ethics application status
Not yet submitted
Date submitted
16/08/2016
Date registered
19/08/2016
Date last updated
27/11/2019
Date data sharing statement initially provided
27/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase II of The Sildenafil during Coronary artery bypass graft Operations to Reduce Endpoints for patients with Coronary ARtery Disease (SCORECARD) Project
Scientific title
Phase II of The Sildenafil during Coronary artery bypass graft Operations to Reduce Endpoints for patients with Coronary ARtery Disease (SCORECARD) Project
Secondary ID [1] 289946 0
None
Universal Trial Number (UTN)
U1111-1186-5405
Trial acronym
The SCORECARD Project
Linked study record
Phase II is a component of the five-arm SCORECARD Project. It is a feasibility study in which the magnitude of the reduction in vasospasm, graft occlusion and ischaemia-reperfusion injury will be calculated in order to determine the sample size required for a future phase III trial of sildenafil vs placebo in patients undergoing CABG. There is currently no ANZCTR number for The SCORECARD Project. AUDITED Numbers (ACTRN12616001114437p) and DESIGNING (ACTRN12616001115426p) are registered.

Health condition
Health condition(s) or problem(s) studied:
Coronary artery disease 299931 0
Condition category
Condition code
Cardiovascular 299830 299830 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients who are randomised to the exposure group will receive sildenafil according to the following regime:
Day before CABG:
sildenafil 50 mg orally three times daily.

Day of CABG:
sildenafil 100 mg orally via nasogastric tube at time of commencement of median sternotomy immediately followed by a 25 mL normal saline flush.
sildenafil 50 mg orally at 22:00.

Postoperatively days 1-28:
sildenafil 50 mg orally three times daily. Sildenafil will be delivered orally but, where not possible (such as immediately postoperatively in the Cardiovascular Intensive Care Unit, will be given via nasogastric tube followed by a 25 mL normal saline flush.

NB: Three 50 mg tablets will be reconstituted with a sweetened solution according to local processes in order to create a 75 mL solution, which is equivalent to 150 mg sildenafil. Patients will be given 25 mL of sildenafil solution three times daily.

Cardiothoracic wards, Cardiovascular Intensive Care Units and patients will all be asked to retain empty patient bottles in the designated SCORECARD box, which will be collected by a SCORECARD Project investigator in order to measure adherence. Unused drug will be retained and, once accounted for by a SCORECARD Project investigator, will be given to the locality pharmacy for disposal according to local processes.
Intervention code [1] 295631 0
Treatment: Drugs
Comparator / control treatment
The comparator treatment in this study will be a placebo solution made up of Ora-Sweet (Registered Trademark) solution also given as 25 mL three times daily. The comparator treatment will be designed to taste and look not dissimilar to the exposure group treatment.
Control group
Placebo

Outcomes
Primary outcome [1] 299305 0
Pulsatility index measured as transit time flowmetry with the MiraQ(TM) Cardiac Unit.
Timepoint [1] 299305 0
Continuous monitoring for up to two minutes immediately after bypass graft anastomosis for each graft anastomosed.
Primary outcome [2] 299306 0
Graft flow in mL per minute as transit time flowmetry with the MiraQ/(TM) cardiac Unit.
Timepoint [2] 299306 0
Continuous monitoring for up to two minutes immediately after bypass graft anastomosis for each graft anastomosed.
Primary outcome [3] 299307 0
Diastolic filling (percentage) as transit time flowmetry using the MiraQ(TM) Cardiac Unit.
Timepoint [3] 299307 0
Continuous monitoring for up to two minutes immediately after bypass graft anastomosis for each graft anastomosed.
Secondary outcome [1] 326793 0
Mortality-rate
Timepoint [1] 326793 0
At 30 days postoperatively.
Secondary outcome [2] 326794 0
Serum Troponin T level measured using LabPLUS protocols.
Timepoint [2] 326794 0
Measured in ng/L at 2, 4, 6, 8, 12, 18, 24, 36 and 48 hours, postoperatively.

Eligibility
Key inclusion criteria
1) Patients who are undergoing CABG +/- valve replacement at Auckland or Waikato District Health Board.
2) Patients who are undergoing CABG +/- valve replacement between 1 February 2017 and 1 February 2018.
3) Patients who are recommended and offered elective CABG +/- valve replacement.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will not be eligible for recruitment if they meet any of the following exclusion criteria:
1) Creatinine clearance less than or equal to 30 mL·min-1.
2) Hepatic failure as determined by Child-Pugh class B or class C.
3) BP less than or equal to 90/50 mm·Hg.
4) Any previous open cardiac surgical procedure.
5) Any history of:
- Pulmonary arterial hypertension.
- Postural hypotension.
- Non-arteritic anterior ischaemic optic neuropathy.
- Hereditary degenerative retinal disorders such as retinitis pigmentosa.
- Recent commencement or increases in alpha blocker dosages.
- Current pregnancy or lactation.
- Allergy to any component of ViagraTM tablet.
6) Any use of sildenafil citrate, tadalafil or vardenafil within the one month prior to enrolment.
7) Any use of glyceryl trinitrate within the previous 24 hours.
8) Concomitant use of isosorbide mononitrate.
9) Concomitant use of potent CYP 3A4 inhibitors:
- Erythromycin.
- Saquinavir.
- Ketoconazole.
- Itraconazole.
- Ritonavir.
10) Presence of any metalware that precludes CMR-use.
11) Unable to provide informed consent.
12) Not eligible for public funding.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
This Feasibility Study will be a double-blind study. The allocation status will be blinded to participants and participants’ clinical teams including their anaesthetist and surgeon. Only the Randomisation Investigator and SCORECARD Pharmacist at each of Auckland and Waikato DHB will have knowledge of participants’ allocation statuses. In the event of emergency unblinding, the Emergency Coordinator will be able to access the patient’s allocation status and may disclose the status to the participant’s clinical team if it s relevant to do so.

Allocation will involve the Principal Investigator contacting the Randomisation Coordinator, who will retain the allocation schedule in a secure firewall-protected database and who is located at a central administration site. The Randomisation Coordinator will update the participant's details and allocation status within the database that is otherwise accessible only to SCORECARD Pharmacists. In this way, allocation statuses will remain blinded.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The purpose of this study is to determine the sample size required in order to determine statistical significance in a future phase III trial.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Study withdrawn.
Date of first participant enrolment
Anticipated
1/02/2017
Actual
Date of last participant enrolment
Anticipated
29/12/2017
Actual
Date of last data collection
Anticipated
1/02/2018
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment outside Australia
Country [1] 8105 0
New Zealand
State/province [1] 8105 0
Auckland and Waikato

Funding & Sponsors
Funding source category [1] 294322 0
University
Name [1] 294322 0
University of Auckland
Country [1] 294322 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
Department of Anaesthesiology
University of Auckland
Private Bag 92019
Auckland 1142
Country
New Zealand
Secondary sponsor category [1] 293161 0
None
Name [1] 293161 0
None
Address [1] 293161 0
None
Country [1] 293161 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 295748 0
Health and Disability Ethics Committee
Ethics committee address [1] 295748 0
Ministry of Health
Ethics Department
Freyberg Building
Reception – Ground Floor
20 Aitken Street
Wellington 6011
Ethics committee country [1] 295748 0
New Zealand
Date submitted for ethics approval [1] 295748 0
01/12/2016
Approval date [1] 295748 0
Ethics approval number [1] 295748 0

Summary
Brief summary
The gold-standard revascularisation approach for patients with left main stem or multi-vessel coronary artery disease (CAD) is coronary artery bypass graft (CABG) surgery. Vasospasm, graft occlusion and ischaemia-reperfusion injury are complications that commonly arise and significantly impact upon CABG success-rates.
Sildenafil is a type 5 phosphodiesterase inhibitor that has vasodilatory, antiplatelet and ischaemia-reperfusion injury-preventing properties. We hypothesise that these properties of sildenafil could be exploited in patients undergoing CABG by reducing vasospasm, graft occlusion and ischaemia-reperfusion injury complication-rates.
The Sildenafil during CABG Operations to Reduce Endpoints for patients with Coronary ARtery Disease (SCORECARD) Project is a novel multi-centre double-blind randomised controlled trial concept in which the vasodilatory, antiplatelet and ischaemia-reperfusion injury-preventing properties of sildenafil will be investigated in elective patients undergoing CABG. However, a population sample that is of sufficient size and power must first be calculated so that a significant difference can be detected in the future trial.
In this feasibility study, a phase II trial will be undertaken in order to establish the magnitude of the difference in outcomes between sildenafil-treated and placebo-treated groups. Two hundred patients admitted under either Auckland or Waikato District Health Board’s cardiothoracic service for elective CABG between 1 February 2017 and 1 February 2018 will be screened against inclusion and exclusion criteria. Patients will be randomised in a double-blind fashion to receive either a sildenafil- or placebo-drug regime. We will collect and compare preoperative and postoperative cardiac magnetic resonance images, transit time flowmetry data, postoperative serum troponin T levels in the first 48 hours and mortality-rates at 30 days.
The results from Phase II of The SCORECARD Project will establish the magnitude of the difference in vasopasm, graft occlusion and ischaemia-reperfusion injury complication-rates between sildenafil-treated and placebo-treated groups. These data will allow for sample size calculations, which will ultimately dictate whether or not it is feasible to proceed with conducting Phase III of The SCORECARD Project.
Trial website
www.scorecard.ac.nz
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 68306 0
Dr Steve Waqanivavalagi
Address 68306 0
Department of Medicine, University of Auckland, Private Bag 92019, Auckland 1142
Country 68306 0
New Zealand
Phone 68306 0
+64275370425
Fax 68306 0
Email 68306 0
[email protected]
Contact person for public queries
Name 68307 0
Dr Steve Waqanivavalagi
Address 68307 0
Department of Medicine, University of Auckland, Private Bag 92019, Auckland 1142
Country 68307 0
New Zealand
Phone 68307 0
+64275370425
Fax 68307 0
Email 68307 0
[email protected]
Contact person for scientific queries
Name 68308 0
Dr Steve Waqanivavalagi
Address 68308 0
Department of Medicine, University of Auckland, Private Bag 92019, Auckland 1142
Country 68308 0
New Zealand
Phone 68308 0
+64275370425
Fax 68308 0
Email 68308 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.